The mammalian stomach has not been studied in any detail in vitro due to lack of a suitable preparation. The piglet gastric mucosa provides this - it is very active and stable physiologically, and it responds quickly to addition and removal of histamine. We propose to study the interactions and relations among divalent cations (specifically Ca and Ba ions), stimulants, inhibitors and ion permeability and transport in this tissue. Electrical potential difference (p.d.), resistance, short circuit current, H plus secretion (pH-stat), and radioisotopic fluxes (C1, Na, and K ions) will be measured in vitro in an Ussing chamber. Intracellular p.d.'s and ionic activities will be measured with microelectrodes. Capacitance elements, calculated from the voltage response to rectangular pulses of current will be compared to known changes in membrane surface area, hopefully allowing method for monitoring apixal and basal membrane area changes. We will study the mechanism and control of the transition between the resting and actively secreting state ("turn on" phase) and in the opposite direction ("turn off"). The relationships between cyclic AMP, Ca ions, and histamine in the control of membrane permeability and re-cycling within oxyntic cells will be explored using the above techniques while independently varying concentrations of the secretagogues and ionic constituents. We are also interested in characterizing the mechanisms of C1- transport, permeation and exchange. Measurement of intracellular p.d.'s and ionic activities as well as the selectivity of anion permeability and transport will be important for a complete characterization of specific cell type and membrane sites involved in C1- transport and exchange. The mechanisms of action of the well-known inhibitors SCN-, acetazolamide, and ouabain will also be investigated and compared to the actions of stimulants as well as the inhibitory actions of Ba ions and high (K plus).